Numerous changes in properties of the cell surface have been associated with important developmental and neoplastic phenomena such as cellular adhesion, growth regulation, tissue invasion, metastasis, and escape from the host immune response. By using defined components, with the model membranes which we have developed, the proposed studies offer the exciting prospect of demonstrating that a specific cell surface molecule is responsible for causing altered membrane function and hence altered cellular social behavior. Membrane structure is monitored with fluorescent probes for mobility and concentration of carbohydrate-bearing molecules. Correlations are made with functional changes in electrical conductance. An apparatus has been constructed for forming and monitoring a simple, spherical model membrane of defined composition. We have demonstrated adhesion between two such membranes made from beef brain gangliosides and egg phosphatidylcholine in n-decane. Gangliosides can provide a transmembrane signal for this functional contact (contact sensation). Without gangliosides, these characteristics were not observed. From the beef brain mixture, we will identify the individual glycolipid responsible for these functions. The role of surface density, Ca++ and neuraminidase-labile sialic acid will be investigated. The force of adhesion will be determined from the transmembrane pressure and the angle of contact. The ions that carry the conductance current will be identified by substitution. Gangliosides from normal and Rous sarcoma virus transformed chicken embryo fibroblasts will be similarly tested for the possible decreased ability of the glycolipids from the transformed cells to mediate adhesion and/or conductance. Regulation of intracellular and membrane-bound Ca++ as a second messenger in response to external stimuli will be confirmed and extended. We will also incorporate gap junction protein into two model membranes in an attempt to demonstrate functional communication between cells. The effect of ganglioside concentration on glycoprotein exposure and antigenicity will be measured in order to model antigenic modulation.